The University of California, Davis (UCD) component (Project I) of this Program Project will be to follow a systematic approach of HIV-1 vaccine development by comparing the immunogenicity and toxicity in guinea pigs and rhesus monkeys of inactivated whole virus and recombinant DNA viral products. The specific aims of Project I (UCD) are: 1) to optimize and standardize conditions for HIV-1 production, purification and inactivation on 10 selected strains of HIV-1 (from Project II-University of California, San Francisco), 2) to assess the immunogenicity and toxicity of whole inactivated HIV and indivdual recombinant viral antigens (from Project III - Chiron Corporation) in guinea pigs and rhesus macaques. Strain-specific humoral and cellular immune responses to the 10 selected HIV-1 isolates will be evaluated, 3) to assess cross-protection from SIV infection and disease in rhesus macaques, immunized with selected HIV strains or antigens, 4) to genetically engineer non-infectious HIV pol gene deletion mutants as candidate whole-virus vaccines and 5) to express HIV-1 envelope glycoproteins and core protein in hybrid vaccinia vectors and infect autologous cell lines as targets for measuring T cell responses in immunized rhesus monkeys.